The influence of neonatally administered capsaicin on the substance P (SP) containing nerves within the nucleus tractus solitarius (NTS), the spinal trigeminal nucleus (NTV), spinal cord and various nuclei in the midbrain and forebrain was studied. Three months after injection the SP content of the dorsal horn of the spinal cord and the NTV was markedly decreased while the NTS and the midbrain and forebrain nuclei were unaffected. Studies of the effect of capsaicin on efflux of SP from tissue slices of NTS, NTV and the hypothalamus revealed that capsaicin elicites release of SP from the NTS and NTV. No alteration of the efflux of SP from hypothalamic slices occurred following capsaicin. The differential sensitivity of neuronal regions to capsaicin suggests a morphological and/or neurochemical difference between sensory and nonsensory SP fibers.